Delivering therapeutic drugs or cell therapies at a controlled release rate to a patient, or delivering encapsulated conductive or magnetic materials at a controlled rate and orientation to process are important goals in medicine and the emerging field of nanotechology manufacturing. Controlling the release of drugs can have a positive effect on therapeutic treatments by maintaining a constant level of the therapy in the patient and also eliminating the need for external intraveneous delivery means or risk of delaying or missing oral administrations of a therapy. Encapsulation can provide enhanced solubility or controlled reactivity for drugs, catalysts, or materials like carbon nanotubes. Micelles and self assembled micelles may allow for the controlled encapsulation and delivery of such materials.
The functional head groups from the molecules which form the micelle and encapsulate the material should interact favorably with the material to be encapsulated. The formed micelle, including the material, must also have the proper reactivity and solubility for its intended application. These properties are determined by the head groups on the molecules which are on the exterior of the micelle as well as the intermolecular bonding of the molecules comprising the micelle. For polar drugs, DNA, mineralizable inorganic salts, and other materials with high surface energies, an encapsulating matrix with a polar core is advantageous.
Bola amphiphiles are molecules in which two or more hydrophilic groups are connected by hydrophobic moieties. Many papers report using peptides as the polar headgroups for symmetrical bola amphiphiles—those in which the head groups are the same. Symmetrical bola-amphiphiles with GlyGly as the hydrophilic headgroups, using saturated hydrocarbon 1,7-heptane dicarboxylic acid have been made (Matsui, H.; Douberly, G. E. Langmuir 2001, 17, 7918-7922, and 1,12-dodecane dicarboxylic acid in Shimizu, T.; Kogiso, M.; Masuda, M. J. Am. Chem. Soc. 1997, 119, 6209-6210). A bola-amphiphile with ValVal as a hydrophilic head group for a bola amphiphile was reported by Kogiso, M.; Hanada, T.; Yase, K.; Shimizu, T. Chem. Comm. 1998, 17, 1791-1792. The dipeptides GlyGly, ProPro, SarSar and (N-methyl)Gly(N-methyl)Gly and the tripeptides GlyGlyGly, GlyProPro, and GlySarSar are the headgroups in a series of bola amphiphiles with 8-16 carbon hydrocarbon diacids as the hydrophobic spacer as reported in Kogiso, M.; Ohnishi, S.; Yase, K.; Masuda, M.; Shimizu, T. Langmuir 1998, 14, 4978-4986. The amino acids Ser, Glu, and Asp have also been reported in bola amphiphiles. Asymmetrical bola amphiphile are those amphiphiles where the hydrophilic groups differ in their hydrophilicity. Some examples of asymmetric bola amphiphiles include sugars, and the nucleosides A and T (Shimizu, T.; Iwaura, R.; Masuda, M.; Hanada, T.; Yase, K. J. Am. Chem. Soc. 2001, 123, 5947-5955). Other examples of asymmetrical bola amphiphiles include those prepared from Lys coupled to 12-amino dodecane carboxylic acid oligomers (Fuhrhop, J. H.; Spiroski, D.; Boettcher, C. J. Am. Chem. Soc. 1993, 115, 1600-1601) in which either rods or tubes are obtained. However, these rods do not bury a polar headgroup within the core of the cylindrical micelle.
There is a need in the art to be able to make self-assembling micelles from amphiphiles that have lyophilic groups at the core and outer surface of the micelle. It would be further desirable to control the structure, reactivity, and function of such micelles by modification of the amphiphile's molecular structure.